PROJECT SUMMARY The objective of the proposed study is to reduce residual morbidity and mortality in pediatric cancer by laying the groundwork for the design of interventions targeting social determinants of health outcomes, specifically poverty. Sequential clinical trials have resulted in steady improvements in survival for children with acute lymphoblastic leukemia (ALL) through incremental advancements in risk stratification and risk-adapted therapy. Despite this achievement, approximately 20% of children with ALL will relapse and 10% will die of their disease making ALL the leading cause of childhood cancer death. One in five children in the United States lives in poverty. Emerging data demonstrate that despite highly standardized care, poverty-related survival disparities exist in childhood ALL in the United States. Mechanisms underlying this relationship have not been defined, nor have targetable domains of poverty been investigated. The hypothesis underlying this proposal is that improved child cancer outcomes are achievable by integrating remediable domains of poverty into risk stratification and developing poverty-targeted interventions. Household material hardship (HMH)?unmet concrete resource needs including food, housing or energy?is a dimension of poverty which predicts general pediatric health outcomes and can be remedied by intervention. Up to 30% of pediatric cancer families report HMH during the first 6 months of chemotherapy; its impact on child cancer outcomes is unknown. A majority of U.S. children diagnosed with acute lymphoblastic leukemia (ALL), the most common childhood cancer, will enroll on a clinical trial. This trial-based paradigm of discovery and care has allowed for steady improvements in biologically-based risk stratification and risk-adapted therapy. Social determinants of health as contributors to outcome have not been systematically incorporated into therapeutic trial design. This proposal leverages an existing clinical trials model of care to investigate the impact of a non-biologic driver of outcome. The specific hypothesis is that HMH impacts pediatric ALL relapse and survival through three mechanisms affecting chemotherapy delivery: (1) Decreased adherence to oral chemotherapy, (2) Inferior underlying child health status leading to chemotherapy toxicity and subsequent delays/dose reductions, and (3) Decreased access to care leading to higher acuity hospital admissions which delay chemotherapy receipt. Building on her pilot work and leveraging the cross-disciplinary expertise of her mentorship team in a mixed methods approach, Dr. Bona proposes to assess whether HMH is associated with inferior disease outcomes in pediatric ALL, and to identify potential mechanisms of action which can be targeted with future interventions. In Aims 1-3) Dr. Bona will embed a prospective survey study of HMH in a phase III multi-center clinical trial for children with newly diagnosed ALL to identify the association between HMH and rates of early relapse and survival (Aim 1), oral chemotherapy adherence (Aim 2a), chemotherapy delivery (Aim 2b) and patterns of care (Aim 3). In Aim 4) Dr. Bona will utilize parent and provider interviews to identify targetable elements in the experience of HMH. Together, these data will inform the subsequent development of an HMH intervention for the clinical trial setting. Poverty crosses all risk group stratifications in pediatric ALL; as such, targeting this predictor of outcomes has the potential to impact a significant proportion of children with cancer. This project will facilitate the candidate's training in three areas central her career development and transition to independence: 1) conduct and design of qualitative research; 2) collaboration on multi-center clinical trials; and 3) understanding the social and biological pathways underlying health inequities. Dr. Bona is pediatric oncologist and outcomes researcher in the richly supportive research setting of the Dana-Farber Cancer Institute (DFCI), an environment ideally suited to the successful conduct of this study. Dr. Bona's research and career development are supported by highly qualified and deeply committed mentors: Dr. Joanne Wolfe, a leader in pediatric palliative care investigation, and Dr. Smita Bhatia a leader in pediatric oncology outcomes research. A dynamic team of advisors with multi-disciplinary expertise in pediatric leukemia, outcomes, disparities, palliative care and psychosocial oncology will oversee the successful conduct of this proposal. Leveraging the research infrastructure of DFCI, the expertise of her mentorship team, and the proposed career development goals Dr. Bona will be well positioned to successfully complete the proposed aims, compete for future R01 funding to support an intervention trial and transition to a career as an independent physician investigator dedicated to reducing health disparities in childhood cancer.